Refractory or relapsing metastatic triple‐negative breast cancer (mTNBC) has a poor prognosis. Sacituzumab govitecan (SG) is a novel antibody‐drug conjugate, targeting human trophoblast cell‐surface antigen 2 (Trop‐2). This is the first report of SG's efficacy and safety in Chinese patients with mTNBC. EVER‐132‐001 (NCT04454437) was a multicenter, single‐arm, Phase IIb study in Chinese patients with mTNBC who failed ≥2 prior chemotherapy regimens. Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21‐day treatment cycle, until disease progression/unacceptable toxicity. The primary endpoint was objective response rate (ORR) assessed by the Independent Review Committee. Secondary endpoints included: duration of response (DOR), clinical benefit rate (CBR), progression‐free survival (PFS), overall survival (OS) and safety. Eighty female Chinese patients (median age 47.6 years; range 24‐69.9 years) received ≥1 SG dose with a median of 8 treatment cycles by the cutoff date (August 6, 2021). Median number of prior systemic cancer treatments was 4.0 (range 2.0‐8.0). ORR and CBR were reported 38.8% (95% confidence interval [CI]: 28.06‐50.30) and 43.8% (95% CI, 32.68‐55.30) of patients, respectively. The median PFS was 5.55 months (95% CI, 4.14‐N/A). SG‐related Grade ≥3 treatment‐emergent adverse events (TEAEs) were reported in 71.3%, the most common were neutrophil count decreased (62.5%), white blood cell count decreased (48.8%) and anemia (21.3%); 6.3% discontinued SG because of TEAEs. SG demonstrated substantial clinical activity in heavily pretreated Chinese patients with mTNBC. The observed safety profile was generally manageable.

Background: The therapeutic options for patients (pts) with previously treated metastatic TNBC are limited compared with other breast cancer subtypes. SKB264 is an antibody drug conjugate (ADC) composed of an anti-TROP2 antibody coupled to the cytotoxic belotecan-derivative via a novel linker. Here, we present results from a Phase 2 expansion cohort for pts with mTNBC (NCT04152499). Methods: Pts with previously treated mTNBC were enrolled to receive SKB264 4 mg/kg Q2W or 5 mg/kg Q2W in a non-randomized fashion until disease progression/unacceptable toxicity. The assessment for tumor response was performed every 8 weeks per RECIST v1.1 assessed by investigator. The TROP2 expression was scored using the semi-quantitative H-score method, and cut off point was set to 200. TROP2 expression and its association with anti-tumor activity was retrospectively analyzed. Results: At data cut-off date (May 15, 2022), 59 pts were enrolled (23 in 4 mg/kg, 36 in 5 mg/kg), 88% of them (52 pts) had received ≥3 prior therapies for metastatic disease. Among 53 patients with tissue available for TROP2 testing, 29 patients (55%) had TROP2 high (H-score >200-300) tumors. The median follow up was 9.6 months. Of 55 pts (21 in 4 mg/kg and 34 in 5 mg/kg) evaluable for response assessment (≥1 on-study scan), the confirmed ORR (cORR) was 40% (22/55) and disease control rate (PR+CR+SD) was 80% (44/55). The cORR was 55% (16/29) in the subset of patients with high TROP2 expression. The median duration of response (DoR) was not reached with range from 1.0+ to 11.0+ months and the 6-month DoR rate was 82%. Median PFS was 5.7 months (95% Cl: 3.9, 7.6). Treatment-related adverse events (TRAEs) of ≥ Grade 3 were reported in 55.9% (33/59) of pts. The most common ≥ Grade 3 TRAEs (≥ 10%) were neutrophil count decreased (23.7%), anemia (20.3%) and platelet count decreased (16.9%). TRAEs led to dose reduction in 15.2% (9/59) of pts and to discontinuation in 6.8% (4/59) of pts. No treatment-related AEs leading to death or interstitial lung disease (ILD) were reported. Safety and anti-tumor activities of SKB264 by dose level will be presented. Conclusions: SKB264 demonstrates a manageable safety profile and promising antitumor activity in pts with heavily pretreated mTNBC. SKB264 toxicity was mainly hematologic. A Phase 3 study of SKB264 vs investigator selected chemo alone in pts with locally advanced inoperable or metastatic TNBC was initiated (NCT05347134). Citation Format: Yongmei Yin, Xinhong Wu, Quchang Ouyang, Min Yan, Lihua Song, YunPeng Liu, Zhongsheng Tong, Cuizhi Geng, Ying Wang, Guohua Yu, Xiang Wang, Ying Cheng, Weihong Zhao, Qun Li, Yina Diao, Gesha Liu, Junyou Ge, Jin Li. Efficacy and safety of SKB264 for previously treated metastatic triple negative breast cancer in Phase 2 study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-03-02.

Background Triple‐negative breast cancer (TNBC) is the most aggressive type of breast cancer. Immune checkpoint inhibitors (ICIs) have been widely used to treat various tumors and have changed the landscape of tumor management, but the data from real‐world studies of ICIs for TNBC treatment remain limited. The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real‐world setting and to explore possible correlates. Methods The clinical data of advanced TNBC patients who received ICI treatment in the Chinese People's Liberation Army (PLA) General Hospital were collected. Treatment responses, outcomes and adverse events (AEs) were assessed. Results Eighty‐one patients were included in the study. The confirmed objective response rate (ORR) was 32.1%, and the disease control rate (DCR) was 64.2%. The median progression‐free survival (PFS) was 4.2 months, and the median overall survival (OS) was 11.0 months. PFS and OS were longer in patients who achieved clinical benefit from ICIs and shorter in patients who received later‐line ICIs and higher levels of inflammation; specifically, patients with higher TILs had longer PFS. Overall AEs were tolerable. Conclusions ICIs are effective in the treatment of advanced TNBC, and the adverse reactions are tolerable. A panel of biomarkers including LDH, ALP, and bNLR were identified to predict the efficacies of ICIs in TNBC treatment.

e13090 Background: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. The lack of specific targets leads in fewer effective treatments and poor prognosis. Immunotherapy has become a new generation of treatment approach in addition to surgery, radiotherapy, chemotherapy, endocrine therapy and targeted therapy. Immune checkpoint inhibitors (ICIs) have been widely used in the clinical treatment of various tumors and changed the landscape of tumor treatment, but the data from real-world studies of ICIs for TNBC remain limited. Methods: Clinical data of patients with advanced TNBC treated with ICIs in Chinese People’s Liberation Army General Hospital were collected from January 2004 to December 2022. The effect of different factors on patient response and prognosis was analyzed using Kaplan-Meier survival curves. The relationship between clinical, pathological characteristics, hematological indicators, and efficiency were analyzed using univariate and multifactorial Cox regressions. Objective Response Rate (ORR), Disease Control Rate (DCR), Progression-free Survival (PFS), Overall survival (OS), and adverse events (AEs) were assessed. Results: Eighty-one patients were enrolled in the study. Median follow-up was 26.3 months (range, 16.0 - 36.6 months). Confirmed ORR was 32.1% and DCR was 64.2%. The median PFS was 4.2 months and the median OS was 11.0 months. Eastern Cooperative Oncology Group (ECOG) performance status score ≥ 1, applying ICIs in 2nd and later lines, with liver metastases, with more than two sites of metastases, lactate dehydrogenase (LDH) ≥ 194.3 U/L, alkaline phosphatase (ALP) ≥ 104.7 U/L, neutrophil-to-lymphocyte ratio at baseline (bNLR) ≥ 2.7, NLR before the second dose of immunotherapy (NLR2) ≥ 2.2, platelet to lymphocyte ratio before the second dose of immunotherapy (PLR2) ≥ 165.6 were associated with a poorer prognosis. Patients with effective initial treatment, tumor - infiltrating lymphocytes (TIL) ≥ 20%, derived neutrophil-to-lymphocyte ratio (dNLR) ≤ 1.9, LDH < 194.3 U/L and bNLR < 2.5 prior to ICI treatment have a better prognosis. Conclusions: ICIs were effective in advanced TNBC with tolerable adverse effects, and we have identified a series of biomarkers associated with PFS and OS. Randomized controlled clinical trials are warranted to validate our findings.

Background: Metronomic chemotherapy, defined as frequent administration of. chemotherapeutic agents at a non-toxic dose without extended rest periods, can overcome drug resistance and achieve disease control with reduced toxicity compared to conventional chemotherapy in maximum tolerated dose by shifting the therapeutic target from tumor cells to tumor endothelial cells. Some of the previous studies of oral vinorelbine have shown good data in efficacy and safety in advanced breast cancer. Methods: The multicenter, open-label, non-inferiority, randomized phase 2 study (NCT03854617) aimed to evaluate the efficacy and safety of oral metronomic vinorelbine in 13 hospitals in China. Eligible HER2-negative breast cancer patients previously treated with anthracycline or taxane regimens were randomized (1:1) to receive metronomic dosage of oral vinorelbine (50mg/3 times a week) or conventional dosage of oral vinorelbine (60mg/m2 weekly for cycle 1 and 80mg/m2 weekly for subsequent cycles in the absence of grade 3 or 4 toxicity) for first-line/second-line chemotherapy. The primary end point was Disease Control Rate (DCR) and a non-inferiority margin of 6% was defined for DCR. Patient characteristics, progression-free survival (PFS), overall survival (OS) and safety/adverse events (AEs) were among the parameters assessed. The expression of 27 cytokines was profiled longitudinally in these patients at baseline and at regular intervals during therapy. Results: Between February 2019 and September 2020, a total of 171 patients were enrolled and randomized to metronomic dosage group (86 patients) and conventional dosage group (85 patients). 136 patients were hormone receptor(HR)positive and 117 patients (68.4%) had visceral metastases. The DCR was 59.3% (95% CI:48.17% to 69.78%) in the metronomic dosage group and 67.1% (95% CI:56.02% to 76.87%) in the conventional dosage group. Whereas, the 18-month survival rate was higher in the metronomic dosage group than that in the conventional dosage group (68.7% vs 43.0%).The median progression-free survival in the metronomic dosage group was 2.8 months (95% CI:1.40 to 3.50) compared with 4.1 months (95% CI:2.80 to 6.20) in the conventional dosage group. Grade 3 or higher adverse events were significantly less frequent in patients in the metronomic dosage group than patients in the conventional dosage group (19.8% vs 48.2%, P&lt;0.001). By comparing the variation of cytokine profiles at baseline and after 6-week treatment in 122 patients, multilevel partial least squares discriminant analysis (PLS-DA) suggested the variation of VEGF, MIP-1α, IL-1B, IL-17, MCP-1, IL-13, PDGF-BB, IL-4 and RANTES were significantly different between the metronomic dosage group and the conventional dosage group during the treatment (all VIP values &gt; 1.2). As for the patients in the metronomic dosage group, GM-CSF, MCP-1, TNF-α, IL-10, IL-13 and MIP-1α were potential biomarkers between the response patients and non-response patients (all VIP values &gt; 1.2). Conclusions: Oral metronomic vinorelbine decreased the risk of severe toxicity significantly and may be an option for older patients and for those intolerable to standard chemotherapy with proper predictive biomarkers, though this study couldn’t prove to show the non-inferiority of oral metronomic vinorelbine for first-line or second-line chemotherapy previously treated with anthracycline or taxane in HER2-negative metastatic breast cancer. Citation Format: Fei Ma, Xinlan Liu, Yanxia Shi, Xiuwen Guan, Huihui Li, Xiaojia Wang, Yuee Teng, Qiang Liu, Jin Yang, Man Li, Qingyuan Zhang, Weihong Zhao, Caiwen Du, Lili Sheng, Binghe Xu. A randomized phase II study investigating oral metronomic vinorelbine versus conventional dosage of vinorelbine in HER2-negative metastatic breast cancer previously treated with anthracycline or taxane:clinical results and biomarker analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-16-02.